What is the treatment course of methotrexate (MTX) in Rheumatoid Arthritis (RA)?

From the Guidelines

Methotrexate should be started at 10–15 mg/week, with escalation of 5 mg every 2–4 weeks up to 20–30 mg/week, depending on clinical response and tolerability, as recommended by the multinational evidence-based recommendations for the use of methotrexate in rheumatic disorders with a focus on rheumatoid arthritis 1. The course of methotrexate in rheumatoid arthritis typically involves:

• Starting with a dose of 10-15 mg/week, with the option to escalate by 5 mg every 2-4 weeks up to 20-30 mg/week, depending on the patient's clinical response and tolerability 1.
• Administering the medication orally, with the possibility of switching to parenteral administration if there is an inadequate clinical response or intolerance 1.
• Supplementing with at least 5 mg of folic acid per week to reduce side effects, as strongly recommended by the experts 1.
• Monitoring the patient's condition regularly, including baseline and periodic complete blood counts, liver function tests, and renal function tests every 1-3 months, to assess the efficacy and safety of the treatment 1.
• Considering combination therapy with other DMARDs or biologics if there is an inadequate response after 3-6 months at optimal dosing 1. Some key points to consider when using methotrexate in rheumatoid arthritis include:
• The importance of patient education and clinical assessment of risk factors for methotrexate toxicity, including alcohol intake 1.
• The need for regular monitoring of liver function, renal function, and complete blood counts to minimize the risk of adverse effects 1.
• The potential for methotrexate to be used as a steroid-sparing agent in certain cases, such as giant-cell arteritis and polymyalgia rheumatica 1.
• The recommendation to avoid using methotrexate during pregnancy or breastfeeding, and to wait at least 3 months after stopping methotrexate before planning a pregnancy 1.

From the FDA Drug Label

In patients with rheumatoid arthritis, effects of methotrexate on articular swelling and tenderness can be seen as early as 3 to 6 weeks Although methotrexate clearly ameliorates symptoms of inflammation (pain, swelling, stiffness), there is no evidence that it induces remission of rheumatoid arthritis nor has a beneficial effect been demonstrated on bone erosions and other radiologic changes which result in impaired joint use, functional disability, and deformity Most studies of methotrexate in patients with rheumatoid arthritis are relatively short term (3 to 6 months). Limited data from long-term studies indicate that an initial clinical improvement is maintained for at least two years with continued therapy.

The course of methotrexate in rheumatoid arthritis typically starts to show effects on articular swelling and tenderness within 3 to 6 weeks. While methotrexate can ameliorate symptoms of inflammation, there is no evidence it induces remission. Most studies are short-term (3 to 6 months), but limited long-term data suggest initial improvements can be maintained for at least 2 years with continued therapy 2. Key points include:

• Effects on articular swelling and tenderness can be seen within 3 to 6 weeks
• Methotrexate can ameliorate symptoms of inflammation
• No evidence of remission induction
• Most studies are short-term
• Initial improvements can be maintained for at least 2 years with continued therapy

From the Research

Course of Methotrexate in Rheumatoid Arthritis

• The starting dosage for methotrexate in patients with rheumatoid arthritis should not be less than 10 mg/week and should be determined based on disease severity and patient-related factors 3.
• When a patient with rheumatoid arthritis shows an inadequate response to methotrexate, the dosage should be increased at intervals of 6 weeks, up to 20 mg/week, according to tolerance and patient-related factors 3.
• Folate supplementation can be given routinely to patients treated with methotrexate for rheumatoid arthritis, with a minimal dosage of 5 mg of folic acid once a week, at a distance from the methotrexate dose 3, 4, 5, 6.
• Folate supplementation has been shown to reduce the incidence of gastrointestinal side effects, hepatotoxicity, and patient withdrawal from methotrexate treatment 5, 6.
• There is no significant difference between high-dose folate and low-dose folate on methotrexate efficacy or toxicity 6.
• Subcutaneous delivery of methotrexate may be considered for patients who experience intolerability or inadequate response to oral methotrexate, with maintenance of the current dosage and titration as needed 7.

Dosage and Administration

• The oral route is preferred when starting methotrexate treatment, with a switch to the intramuscular or subcutaneous route considered in patients with poor compliance, inadequate effectiveness, or gastrointestinal side effects 3.
• Methotrexate dosage should be maintained when switching from oral to subcutaneous delivery, with titration as needed 7.
• Treatment with oral methotrexate should be continued for at least 6 months to achieve an accurate assessment of treatment efficacy 7.

Monitoring and Safety

• Investigations that are mandatory for monitoring methotrexate therapy in patients with rheumatoid arthritis consist of full blood cell counts and serum transaminase and creatinine assays, which should be obtained at least once a month for the first 3 months then every 4-12 weeks 3.
• In the event of respiratory symptoms possibly related to methotrexate toxicity, the drug must be stopped and symptom severity evaluated 3.